The long range objective of this proposal is to find mild, highly specific conditions for the targeted addition of polyethylene glycol to specific residues of recombinant proteins. Because proteins which have been modified by polyethylene glycol addition have increased serum persistence and decreased immunogenicity, this objective, if achieved, has the potential to decrease the frequency of parenteral administration of recombinant proteins, and may allow larger and more complex biological structures, such as viruses of cells, to be modified so as to increase their biological half life and decrease the rate at which they are removed or destroyed by the immune system. Much of the work proposed is aimed at obtaining precise information about the behavior of small model compounds which mimic the polyethylene glycol substituents intended for ultimate use.